title: Advanced glycation end products impair glucose-induced insulin secretion from rat pancreatic β-cells.
abstract: BACKGROUND
  Advanced glycation end products (AGEs) are derivative compounds generated from non-enzymatic glycosylation and oxidation. In comparison with glucose-derived AGEs (Glu-AGEs), glyceraldehyde-derived AGEs (Glycer-AGEs) have stronger toxicity to living systems. In this study, we compared the effects of Glu-AGE and Glycer-AGE on insulin secretion.
  
  
  METHODS
  Rat pancreatic islets were isolated by collagenase digestion and primary-cultured in the presence of 0.1 mg/ml bovine serum albumin (BSA) or 0.1 mg/ml Glu-AGE or Glycer-AGE-albumin. After 48 h of culture, we performed an insulin secretion test and identified the defects by a battery of rescue experiments [corrected]. Also, mRNA expression of genes associated with insulin secretion was measured.
  
  
  RESULTS
  Insulin secretion induced by a high glucose concentration was 164.1 ± 6.0, 124.4 ± 4.4 (P < 0.05) and 119.8 ± 7.1 (P < 0.05) μU/3 islets/h in the presence of BSA, Glu-AGE, and Glycer-AGE, respectively. Inhibition of insulin secretion by Glu-AGE or Glycer-AGE was rescued by a high extracellular potassium concentration, tolbutamide and α-ketoisocaproic acid, but not by glyceraldehyde, dihydroxacetone, methylpyruvate, glucagon-like peptide-1 and acetylcholine. Glu-AGE or Glycer-AGE reduced the expression of the malate dehydrogenase (Mdh1/2) gene, which plays a critical role in the nicotinamide adenine dinucleotide (NADH) shuttle.
  
  
  CONCLUSIONS
  Despite its reported cytotoxicity, the effects of Glycer-AGE on insulin secretion are similar to those of Glu-AGE.
authors.affiliation: Second Department of Surgery, Dokkyo Medical University, School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan. hachiya8@dokkyomed.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hachiya
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Miura
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Park
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kubota
mesh_terms: D000818:Animals; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000502:physiology*; D005985:Glyceraldehyde / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology; D008291:Malate Dehydrogenase / Q000235:genetics; D008297:Male; D011188:Potassium / Q000502:physiology; D011773:Pyruvates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017127:Glycation End Products, Advanced; D007328:Insulin; D007651:Keto Acids; D011773:Pyruvates; D005985:Glyceraldehyde; C104813:methyl pyruvate; C013082:alpha-ketoisocaproic acid; D008291:Malate Dehydrogenase; D005947:Glucose; D011188:Potassium
keywords: Advanced glycation end products · Insulin secretion · Nicotinamide adenine dinucleotide shuttle